Context: Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal
polypeptide (VIP) are found in the ovary of mammalian species, although nothing is known about
the possible role of PACAP and VIP in the human ovary.
Objective:Weinvestigated the expression ofPACAPand PACAP/VIP receptors inhumangranulosaluteal
(GL) cells obtained from consenting in vitro fertilization patients attending a private fertility
clinic and assessed a possible antiapoptotic effect of these molecules.
Main Outcome Measures: We measured the expression of PACAP and PACAP/VIP receptor mRNAs
in GL cells in response to FSH or LH, as well as the effects of PACAP and VIP on apoptosis. We also
evaluated the levels of procaspase-3 in GL cells cultured in the absence of serum.
Results: After 7 d inculture, GL cells displayed increased responsiveness to FSH and LH (100 ng/ml).
FSH and LH promoted PACAP expression, LH doing so in a time-dependent fashion. VIP receptor
(VPAC1-R and VPAC2-R) mRNAs were also induced by gonadotropin stimulation. Although PACAP
receptor (PAC1-R) mRNA was barely detectable, Western blot analysis revealed its presence. The
apoptotic effect of serum withdrawal from the culture environment was reverted by both PACAP
and VIP. Both peptides showed the ability to reverse a decrease in procaspase-3 levels induced by
culture in the absence of serum.
Conclusions: PACAP and VIP appear to play a role in maintenance of follicle viability as a consequence
of the antiapoptotic effect. Further studies are warranted to evaluate the respective roles
ofPACAPandVIP in ovarian physiologyandto identify theirmechanismof action. (J Clin Endocrinol
Metab 93: 4924–4932, 2008)

Context: Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal
polypeptide (VIP) are found in the ovary of mammalian species, although nothing is known about
the possible role of PACAP and VIP in the human ovary.
Objective:Weinvestigated the expression ofPACAPand PACAP/VIP receptors inhumangranulosaluteal
(GL) cells obtained from consenting in vitro fertilization patients attending a private fertility
clinic and assessed a possible antiapoptotic effect of these molecules.
Main Outcome Measures: We measured the expression of PACAP and PACAP/VIP receptor mRNAs
in GL cells in response to FSH or LH, as well as the effects of PACAP and VIP on apoptosis. We also
evaluated the levels of procaspase-3 in GL cells cultured in the absence of serum.
Results: After 7 d inculture, GL cells displayed increased responsiveness to FSH and LH (100 ng/ml).
FSH and LH promoted PACAP expression, LH doing so in a time-dependent fashion. VIP receptor
(VPAC1-R and VPAC2-R) mRNAs were also induced by gonadotropin stimulation. Although PACAP
receptor (PAC1-R) mRNA was barely detectable, Western blot analysis revealed its presence. The
apoptotic effect of serum withdrawal from the culture environment was reverted by both PACAP
and VIP. Both peptides showed the ability to reverse a decrease in procaspase-3 levels induced by
culture in the absence of serum.
Conclusions: PACAP and VIP appear to play a role in maintenance of follicle viability as a consequence
of the antiapoptotic effect. Further studies are warranted to evaluate the respective roles
ofPACAPandVIP in ovarian physiologyandto identify theirmechanismof action. (J Clin Endocrinol
Metab 93: 4924–4932, 2008)